There is currently no reliable therapy and no cure for tinnitus. NeuroSystec, in collaboration with basic and clinical scientists at the Kresge Hearing Research Institute (KHRI) and the Medical University of Hannover (MHH), has: 1) confirmed that gacyclidine (NST-001) is effective in animal models for tinnitus and 2) suppresses human tinnitus through compassionate therapy. However, for effective and practical tinnitus control, NST-001 must be formulated for chronic and long-term administration. In this regard, NST-001 is not sufficiently stable; not sufficiently soluble; and suffers from problems of loss to catheters and other components of delivery systems during administration. In a breakthrough discovery, NeuroSystec has developed a solid drug-delivery device which solves the problems of sustained and long-term administration of NST-001. However, while this technology will allow therapy for many patients, it will still suffer from problems associated with drug loss in those patients who have been fitted with a cochlear implant (CI). The materials used to fabricate CIs will adsorb a substantial fraction of NST-001 from solutions, when these solutions are administered through or near the CI. To solve this drug delivery problem, NeuroSystec plans to employ a nanoparticle formulation of the drug to: 1) keep the drug in a stable suspension capable of passing through a proprietary antibacterial filter; and 2) avoid loss of drug to CI components during or after release into the cochlea. To achieve this end, NeuroSystec plans to meet the following goals during the period of the proposed project: Specific aim 1. Improve existing mixing technology to be used in the solvent-displacement method for nanoparticles fabricated from GMP materials that are approved for human implantation [e.g., poly(lactide-co-glycolide), PLGA or equivalent material] and to co-formulate nanoparticles with light oils (triglycerides) to adjust their densities, sedimentation times and drug-binding properties. Specific aim 2. Develop methodologies for loading nanoparticles with NST-001 after fabrication that would allow for use of the formulation in patients fitted with a CI. Specific aim 3. Develop methodologies for loading nanoparticles with NST-001 concurrently with nanoparticle fabrication (the conventional method). [unreadable] [unreadable] [unreadable]